1. Field of the Invention
The present invention relates to contrast medium composition and a method of bio imagination using the same.
2. Background of the Invention
Sentinel lymph nodes (SLNs) are the first lymph nodes which cancer cells reach after traveling through lymphatic vessels from the primary tumor. Evaluating the nodal status is crucial in accurate staging of human cancers and accordingly determines prognosis and the most appropriate treatment. While patients with breast cancer and melanoma are currently subject to invasive sentinel lymph node biopsy (SLNB) to stage metastases, alternative noninvasive methods have been pursued. In particular, noninvasive imaging methods based on the blue dyes and radioactive colloids are the major methods for identification of SLNs in clinical research since they were introduced about two decades ago. Although these methods are being used widely, there are drawbacks in each method. Owing to the spectral limit of the blue dyes, SLNs cannot be identified without a skin incision. Since the dyes are small sized molecules, they are quickly drained from the initial loading point. This rapid diffusion property, however, becomes disadvantageous for staying in the SLN area surrounded by permeable lymphatic vessels. After short retention in SLN (ca. 15-20 min), the dyes pass to secondary nodes, causing difficulties in distinguishing selectively SLNs from other subsequent nodes. Recently, indocyanine green (ICG), a near infrared (NIR) dye, has been employed to circumvent the optical drawback of the blue dyes. While improvement in macroscopic detection of SLNs was achieved by using ICG, the short retention issue could not be addressed since ICG is also a small dye. In contrast to the small dye-based imaging agents, the radioisotope-labeled colloids including the 99mTc-labeled sulfur colloid have a relatively slow diffusion rate and thus tend to remain at the site of administration. Because of this slow diffusion, it takes a long time for the colloids to arrive at a lymph node and should therefore be injected the day before the operation for lymphatic mapping. Additionally, this radioisotope method can be used in limited places because of the safety regulations for radioactive agents. To overcome these drawbacks observed in the conventional dye-guided or radio-guided SLN mapping methods, noninvasive imaging modalities such as ultrasound, computed tomography (CT), magnetic resonance imaging, optical imaging, photoacoustic tomography have been investigated for identification of SLNs. These newly studied methods utilize mainly nanoparticle-based imaging agents, since they show relatively quick arrival at the lymph node site compared to the colloids of radionuclide and extended retention time at the SLN area compared to the small dyes. Inorganic or polymer nanoparticles, however, have a potential to be toxic in vivo since they are made from biologically unnatural materials.
Previously, it has been shown that inherently biocompatible DNA could self-assemble to construct various three dimensional (3D) DNA nanocages including tetrahedra, bipyrimids, octahedra, dodecahedra and fullerene-like structures. Among them, the DNA tetrahedron has been considered one of the most practical DNA nanocages since it can be assembled simply from four DNA strands and prepared in high yield. The recent demonstration about cellular uptake of the DNA tetrahedron into mammalian cells has opened a great opportunity for the nanocage to play important roles in biomedical applications. In addition, the tetrahedron is significantly nuclease resistant, which makes the DNA tetrahedron even a more attractive tool for in vivo imaging technology. Although previous studies demonstrated that the DNA nanocages could become a promising tool for studying biotechnology such as drug delivery and stimulation of immune response at an in vitro cellular level, in vivo applications of the 3D DNA nanoconstructs is still in its infancy. Regarding this, siRNA-loaded DNA tetrahedra were very recently developed and used for effective mRNA regulation in an in vivo system as a pioneering study.
This application seeks priority to and incorporates by reference the following U.S. pending provisional patent applications. Methods and materials similar or equivalent to those described herein can be used in the practice or testing of embodiments of the present invention. All publications mentioned herein are incorporated by reference in their entirety. The documents, patents and patent applications referred to herein are hereby incorporated by reference.